公开(公告)号：US08541548B2

公开(公告)日：2013-09-24

申请号：US12140751

申请日：2008-06-17

申请人： David B. Rozema

发明人： David B. Rozema

IPC分类号： A61K38/00 ,  C07K1/00

CPC分类号： C07D495/04 ,  A01K2217/058 ,  A01K2267/0362 ,  A61K48/0041 ,  C07C233/21 ,  C07C233/31 ,  C07C233/39 ,  C07D307/60 ,  C07D475/00 ,  C12N15/87

摘要： The present invention is directed compounds for reversibly modification of biologically active molecules. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of reversible modification provides for physiologically responsive activity modulation.

摘要翻译： 本发明涉及可逆地修饰生物活性分子的化合物。 描述了将靶向，抗调理作用，抗聚集和转染活性结合到小的生物相容性体内递送缀合物中的多偶联体系。 使用可逆修饰提供了生理反应活性调节。

公开(公告)号：US08017109B2

公开(公告)日：2011-09-13

申请号：US12140703

申请日：2008-06-17

申请人： Darren H. Wakefield ,  David B. Rozema ,  Sean D. Monahan ,  Lori Higgs ,  Jon A. Wolff ,  James E. Hagstrom

发明人： Darren H. Wakefield ,  David B. Rozema ,  Sean D. Monahan ,  Lori Higgs ,  Jon A. Wolff ,  James E. Hagstrom

IPC分类号： A61K31/74

CPC分类号： C12N15/87 ,  A01K2217/058 ,  A01K2267/0362 ,  A61K47/58

摘要： The present invention is directed to membrane active polymers useful for cellular delivery of compounds. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of reversible modification provides for physiologically responsive activity modulation.

摘要翻译： 本发明涉及可用于细胞递送化合物的膜活性聚合物。 描述了将靶向，抗调理作用，抗聚集和转染活性结合到小的生物相容性体内递送缀合物中的多偶联体系。 使用可逆修饰提供了生理反应活性调节。

公开(公告)号：US07871818B2

公开(公告)日：2011-01-18

申请号：US10765668

申请日：2004-01-27

申请人： David B. Rozema ,  Darren Wakefield

发明人： David B. Rozema ,  Darren Wakefield

IPC分类号： C12N15/00 ,  C12N15/09 ,  A61K9/14

CPC分类号： A61K47/58

摘要： We describe a class of polymaleic anhydride polymers capable of disrupting cell membranes. Co-delivery of these polymers with biologically active compounds increases cellular cytoplasmic delivery of the compounds.

摘要翻译： 我们描述了一类能够破坏细胞膜的聚马来酸酐聚合物。 这些聚合物与生物活性化合物的共同递送增加化合物的细胞胞质递送。

公开(公告)号：US07148205B2

公开(公告)日：2006-12-12

申请号：US10600290

申请日：2003-06-20

申请人： Sean D. Monahan ,  Jon A. Wolff ,  Paul M. Slattum ,  James E. Hagstrom ,  Vladimir G. Budker ,  David B. Rozema

发明人： Sean D. Monahan ,  Jon A. Wolff ,  Paul M. Slattum ,  James E. Hagstrom ,  Vladimir G. Budker ,  David B. Rozema

IPC分类号： A61K31/70 ,  C07H21/04

CPC分类号： C12N15/87 ,  A61K31/70 ,  A61K47/59 ,  A61K47/593 ,  A61K47/645 ,  A61K48/00 ,  A61K48/0083 ,  C07H21/00 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/3233 ,  C12N2320/32 ,  A61K2300/00

摘要： Disclosed is a process for transfecting genetic material into a mammalian cell to alter endogenous properties of the cell. The process comprises designing a polynucleotide for transfection. Then the polynucleotide is inserted into a mammalian vessel such as a tail vein or artery. Prior to insertion, subsequent to insertion, or concurrent with insertion the permeability of the vessel is increased thereby the genetic material is delivered to the parenchymal cell altering endogenous properties of the cell.

公开(公告)号：US07087770B2

公开(公告)日：2006-08-08

申请号：US09779791

申请日：2001-02-08

申请人： Jon A. Wolff ,  Sean D. Monahan ,  Vladimir G. Budker ,  Paul M. Slattum ,  David B. Rozema

发明人： Jon A. Wolff ,  Sean D. Monahan ,  Vladimir G. Budker ,  Paul M. Slattum ,  David B. Rozema

IPC分类号： C11D1/60 ,  A61K9/127 ,  C12N15/88

CPC分类号： A61K48/00 ,  A61K31/155 ,  A61K31/198 ,  A61K38/08 ,  C07C323/60 ,  C07C323/62 ,  C07D207/46 ,  C07H21/04

摘要： A labile disulfide-containing compound under physiological conditions containing a labile disulfide bond and a transduction signal.

摘要翻译： 含有不稳定二硫键和转导信号的生理条件下的不稳定二硫键化合物。

公开(公告)号：US06379966B2

公开(公告)日：2002-04-30

申请号：US09450315

申请日：1999-11-29

申请人： Sean D. Monahan ,  Jon A. Wolff ,  Paul M. Slattum ,  James E. Hagstrom ,  Vladimir G. Budker ,  David B. Rozema

发明人： Sean D. Monahan ,  Jon A. Wolff ,  Paul M. Slattum ,  James E. Hagstrom ,  Vladimir G. Budker ,  David B. Rozema

IPC分类号： C12N1585

CPC分类号： A61K48/0041 ,  A61K48/0008 ,  A61K48/0083

摘要： Disclosed is a complex for providing nucleic acid expression in a cell. A polynucleotide and a polymer are mixed together to form the complex wherein the zeta potential of the complex is not positive. Then the complex is delivered to the cell wherein the nucleic acid is expressed.

摘要翻译： 公开了用于在细胞中提供核酸表达的复合物。 将多核苷酸和聚合物混合在一起形成复合物，其中络合物的ζ电位不是正的。 然后将复合物递送到其中表达核酸的细胞。

公开(公告)号：US20130317079A1

公开(公告)日：2013-11-28

申请号：US13592403

申请日：2012-08-23

申请人： Darren H. Wakefield ,  David B. Rozema ,  Nicholas Rossi ,  Lauren Almeida ,  Anthony L. Perillo-Nicholas

发明人： Darren H. Wakefield ,  David B. Rozema ,  Nicholas Rossi ,  Lauren Almeida ,  Anthony L. Perillo-Nicholas

IPC分类号： A61K47/32

CPC分类号： B25F5/02 ,  A61K47/32 ,  A61K47/58 ,  B23D45/16 ,  B23Q13/00 ,  B27B5/29 ,  B27B9/00 ,  C08F220/00 ,  C08F220/34 ,  C08F220/36 ,  C08F220/18

摘要： The present invention is directed membrane active poly(acrylate) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides cells in vivo. RNAi polynucleotides are conjugated to the poly(acrylate) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(acrylate) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.

公开(公告)号：US20130245091A1

公开(公告)日：2013-09-19

申请号：US13615938

申请日：2012-09-14

申请人： David B. Rozema ,  David L. Lewis ,  Darren H. Wakefield ,  Torsten Hoffmann ,  Eric A. Kitas ,  Peter Mohr ,  Philipp Hadwiger ,  Wilma Thuer ,  Linda Valis

发明人： David B. Rozema ,  David L. Lewis ,  Darren H. Wakefield ,  Torsten Hoffmann ,  Eric A. Kitas ,  Peter Mohr ,  Philipp Hadwiger ,  Wilma Thuer ,  Linda Valis

IPC分类号： A61K47/32 ,  A61K47/48

CPC分类号： C12N15/113 ,  A61K9/08 ,  A61K31/713 ,  A61K47/32 ,  A61K47/549 ,  A61K47/60 ,  A61K47/65 ,  A61K48/0041 ,  C12N15/111 ,  C12N15/87 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/3515 ,  C12N2320/32

摘要： The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.

公开(公告)号：US08501930B2

公开(公告)日：2013-08-06

申请号：US13326433

申请日：2011-12-15

申请人： David B. Rozema ,  Darren H. Wakefield ,  David L. Lewis ,  Jon A. Wolff ,  Andrei V. Blokhin ,  Jonathan D. Benson ,  Jeffrey C. Carlson ,  Philipp Hadwiger ,  Eric A. Kitas ,  Torsten Hoffmann ,  Kerstin Jahn-Hofmann ,  Peter Mohr ,  Hans Martin Mueller ,  Guenther Ott ,  Ingo Roehl

发明人： David B. Rozema ,  Darren H. Wakefield ,  David L. Lewis ,  Jon A. Wolff ,  Andrei V. Blokhin ,  Jonathan D. Benson ,  Jeffrey C. Carlson ,  Philipp Hadwiger ,  Eric A. Kitas ,  Torsten Hoffmann ,  Kerstin Jahn-Hofmann ,  Peter Mohr ,  Hans Martin Mueller ,  Guenther Ott ,  Ingo Roehl

IPC分类号： C07H21/04 ,  C07H21/02 ,  C07K5/00

CPC分类号： A61K47/48261 ,  A61K47/549 ,  A61K47/64 ,  A61K47/6415 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/351 ,  C12N2310/3515 ,  C12N2320/32

摘要： The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted melittin delivery peptides. Delivery peptides provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery peptides.

公开(公告)号：US08426554B2

公开(公告)日：2013-04-23

申请号：US13336028

申请日：2011-12-23

申请人： David B. Rozema ,  Darren H. Wakefield ,  David L. Lewis ,  Jon A. Wolff ,  Andrei V. Blokhin ,  Jonathan D. Benson ,  Jeffrey C. Carlson ,  Philipp Hadwiger ,  Eric A. Kitas ,  Torsten Hoffmann ,  Kerstin Jahn-Hoffmann ,  Peter Mohr ,  Hans Martin Mueller ,  Guenther Ott ,  Ingo Roehl

发明人： David B. Rozema ,  Darren H. Wakefield ,  David L. Lewis ,  Jon A. Wolff ,  Andrei V. Blokhin ,  Jonathan D. Benson ,  Jeffrey C. Carlson ,  Philipp Hadwiger ,  Eric A. Kitas ,  Torsten Hoffmann ,  Kerstin Jahn-Hoffmann ,  Peter Mohr ,  Hans Martin Mueller ,  Guenther Ott ,  Ingo Roehl

IPC分类号： C07K16/00

CPC分类号： A61K38/00 ,  A61K31/7088 ,  A61K47/60 ,  A61K47/65 ,  A61K48/00 ,  C07C69/96 ,  C07C271/20 ,  C07H15/04 ,  C07H15/20 ,  C07H15/26 ,  C07K7/02 ,  C07K2317/77 ,  C12N15/1138 ,  C12N15/87 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/351 ,  C12N2320/30

摘要： The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.

摘要翻译： 本发明涉及用于将RNA干扰（RNAi）多核苷酸递送至细胞体内的组合物。 组合物包含用酶切割二肽 - 氨基苄基 - 碳酸酯掩蔽剂可逆地修饰的两亲膜活性多胺。 改性掩盖聚合物的膜活性，而可逆性提供生理反应性。 可逆修饰的多胺（动态多偶联物或DPC）进一步与RNAi多核苷酸共价连接，或与靶向RNAi多核苷酸靶向分子缀合物共同施用。